Nasopharyngeal Carriage of Streptococcus pneumoniae Serotypes Among Healthy Children in Northern India.

Streptococcus pneumoniae (SP) infections cause morbidity and mortality among children worldwide. Hence India introduced 13-valent pneumococcal conjugate vaccine (PCV-13) in 2017 in a phased manner. The primary objective of this study was to assess the proportion of healthy children having nasopharyngeal colonization (NP) with SP. Secondary objective was to determine prevalent serotype of SP among the PCV13 vaccinated and non-vaccinated children. This cross-sectional study was conducted in 4 hospitals of Lucknow District, Northern India. Three hundred healthy children (2-59 months) were recruited between July and August 2019 from vaccination-clinics of hospitals. NP specimen was cultured using 5% sheep blood agar plate containing gentamicin. Pneumococcal isolates were identified by optochin sensitivity and bile-solubility tests. Serotyping was done using Quellung Method. Of the 300 healthy children, 56.7% (170/300) were males and 59.3% (181/300) had received at least one dose of PCV13 vaccine. The NP carriage rate of SP among healthy children was 37.7% (113/300). Vaccine serotypes were found in 33.3% (22/66) in PCV vaccinated children and 48.9% (23/47) in non-vaccinated children (p 0.09). Common vaccine serotypes that isolated were: 18C, 19A, 19F, 23F, 3, 4, 6A, 6B, 9 V. Thus more than one-third of healthy children had NP colonization with SP. Adjusting for age, there was a trend for significant reduction in vaccine serotypes in the NP with one doses versus two or more doses (ptrend = 0.04).

Reproducibility of systematic literature reviews on food, nutrition, physical activity and endometrial cancer.

OBJECTIVE: Despite the increasing dependence on systematic reviews to summarise the literature and to issue public health recommendations, the formal assessment of the reliability of conclusions emerging from systematic reviews has received little attention. The main goal of the present study was to evaluate whether two independent centres, in two continents, draw similar conclusions regarding the association of food, nutrition and physical activity and endometrial cancer, when provided with the same general instructions and with similar resources. DESIGN: The assessment of reproducibility concentrated on four main areas: (1) paper search and selection; (2) assignment of study design; (3) inclusion of papers; and (4) individual studies selected for meta-analysis and the summary risk estimate obtained. RESULTS: In total 310 relevant papers were identified, 166 (54 %) were included by both centres. Of the remaining 144 papers, 72 (50 %) were retrieved in the searches of one centre and not the other (54 in centre A, 18 in centre B) and 72 were retrieved in both searches but regarded as relevant by only one of the centres (52 in centre A, 20 in centre B). Of papers included by both centres, 80 % were allocated the same study design. Agreement for inclusion of cohort-type and case-control studies was about 63% compared with 50% or less for ecological and case series studies. The agreement for inclusion of 138 'key' papers was 87 %. Summary risk estimates from meta-analyses were similar. CONCLUSIONS: Transparency of process and explicit detailed procedures are necessary parts of a systematic review and crucial for the reader to interpret its findings.

Bidi and cigarette smoking and risk of acute myocardial infarction among males in urban India.

Death from myocardial infarction (MI) in India is exacerbated by smoking of bidis or cigarettes. Smoking among 309 men with incident MI was compared to 618 age matched controls; 56% of the individuals with MI and 26% of controls were current smokers. Current smokers had a relative risk of 4.7 (95% confidence interval (CI) 3.2 to 6.9) compared to never smokers. Relative risks for smoking more than 10 cigarettes or 10 bidis daily were 9.1 (95% CI 4.7 to 17.7) and 8.1 (95% CI 4.3 to 15.3), respectively. It is estimated that smoking may cause 53% (95% CI 47% to 64%) of MIs among urban males in India.

Smaller, faster ribozymes reveal the catalytic core of Neurospora VS RNA.

We have investigated the structural requirements for cis-cleavage of the VS ribozyme by designing deletions, substitutions, and circular permutations based on the secondary structure model. Four of the six helices predicted in the model have been shortened, resulting in self-cleaving RNAs of only 121 to 126 nucleotides. Remarkably, the shorter ribozymes exhibit a 30 to 40-fold faster cis-cleavage rate. The increase in activity results from disrupting an inhibitory helix whose 5' side contains bases upstream of the cleavage site, and from constructing a circular permutation that tethers the helix containing the cleavage site to a shortened version of the rest of the ribozyme. The non-essential regions identified by the deletions map to the periphery of a recently proposed structure model, revealing a central ribozyme core that contains the essential structural elements required for activity of the VS ribozyme.

A long-range pseudoknot is required for activity of the Neurospora VS ribozyme.

Four small RNA self-cleaving domains, the hammerhead, hairpin, hepatitis delta virus and Neurospora VS ribozymes, have been identified previously in naturally occurring RNAs. The secondary structures of these ribozymes are reasonably well understood, but little is known about long-range interactions that form the catalytically active tertiary conformations. Our previous work, which identified several secondary structure elements of the VS ribozyme, also showed that many additional bases were protected by magnesium-dependent interactions, implying that several tertiary contacts remained to be identified. Here we have used site-directed mutagenesis and chemical modification to characterize the first long-range interaction identified in VS RNA. This interaction contains a 3 bp pseudoknot helix that is required for tertiary folding and self-cleavage activity of the VS ribozyme.

Enhancement of Neurospora VS ribozyme cleavage by tuberactinomycin antibiotics.

Several examples of inhibition of the function of a ribozyme or RNA-protein complex have shown that certain antibiotics can interact specifically with RNA. There are, however, few examples of antibiotics that have a positive, rather than a negative, effect on the function of an RNA. We have found that micromolar concentrations of viomycin, a basic, cyclic peptide antibiotic of the tuberactinomycin group, enhance the cleavage of a ribozyme derived from Neurospora VS RNA. Viomycin decreases by an order of magnitude the concentration of magnesium required for cleavage. It also stimulates an otherwise insignificant transcleavage reaction by enhancing interactions between RNA molecules. The ability of viomycin to enhance some RNA-mediated reactions but inhibit others, including translation and Group I intron splicing, demonstrates the potential for natural selection by small molecules during evolution in the 'RNA world' and may have broader implications with respect to ribozyme expression and activity in contemporary cells.